Drugging the undruggable: Advances in targeting KRAS signaling in solid tumors.

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Prajna Tripathi, Rajni Kumari, Rajiv Pathak
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引用次数: 0

Abstract

Cancer remains the leading cause of global mortality, prompting a paradigm shift in its treatment and outcomes with the advent of targeted therapies. Among the most prevalent mutations in RAS-driven cancers, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for approximately 86% of cases worldwide, particularly in lung, pancreatic, and colon cancers, contributing to poor prognosis and reduced overall survival. Despite numerous efforts to understand the biology of KRAS mutants and their pivotal role in cancer development, the lack of well-defined drug-binding pockets has deemed KRAS an "undruggable" therapeutic target, presenting significant challenges for researchers and clinicians alike. Through significant biochemical and technological advances, the last decade has witnessed promising breakthroughs in targeted therapies for KRAS-mutated lung, colon, and pancreatic cancers, marking a critical turning point in the field. In this chapter, we provide an overview of the characteristics of KRAS mutations across various solid tumors, highlighting ongoing cutting-edge research on the immune microenvironment, the development of KRAS-driven mice models, and the recent progress in the exploration of specific KRAS mutant-targeted therapeutic approaches. By comprehensive understanding of the intricacies of KRAS signaling in solid tumors and the latest therapeutic developments, this chapter will shed light on the potential for novel therapeutic strategies to combat KRAS-driven tumors and improve patient outcomes.

药到病除:针对实体瘤 KRAS 信号的研究进展。
癌症仍然是导致全球死亡的主要原因,随着靶向疗法的出现,癌症的治疗模式和结果发生了转变。在 RAS 驱动型癌症中最常见的突变中,Kirsten 大鼠肉瘤病毒癌基因同源体(KRAS)突变约占全球病例的 86%,尤其是在肺癌、胰腺癌和结肠癌中,导致预后不良和总生存率降低。尽管人们为了解 KRAS 突变体的生物学特性及其在癌症发展中的关键作用做出了大量努力,但由于缺乏明确的药物结合口袋,KRAS 被认为是一个 "不可药用 "的治疗靶点,这给研究人员和临床医生带来了巨大挑战。通过重大的生化和技术进步,过去十年见证了针对 KRAS 基因突变的肺癌、结肠癌和胰腺癌的靶向疗法取得了可喜的突破,标志着该领域的一个关键转折点。在本章中,我们将概述各种实体瘤中 KRAS 突变的特点,重点介绍正在进行的有关免疫微环境的前沿研究、KRAS 驱动小鼠模型的开发以及在探索特定 KRAS 突变靶向治疗方法方面的最新进展。通过全面了解实体瘤中 KRAS 信号转导的复杂性和最新治疗进展,本章将阐明新型治疗策略的潜力,以对抗 KRAS 驱动的肿瘤并改善患者预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International review of cell and molecular biology
International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
7.70
自引率
0.00%
发文量
67
审稿时长
>12 weeks
期刊介绍: International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
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